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A nonsense mutation in the LIMP-2 gene associated with progressive myoclonic epilepsy and nephrotic syndrome

2008-07-15Artigo científico Acesso aberto
http://hdl.handle.net/10400.16/885
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Autores

Balreira, A.
Gaspar, P.
Caiola, D.
Chaves, J.
Beirão, I.
Lima, J.
Azevedo, J.
Miranda, M.

Orientador(es)

Resumo(s)

Abstract The main clinical features of two siblings from a consanguineous marriage were progressive myoclonic epilepsy without intellectual impairment and a nephrotic syndrome with a strong accumulation of C1q in capillary loops and mesangium of kidney. The biochemical analysis of one of the patients revealed a normal beta-glucocerebrosidase activity in leukocytes, but a severe enzymatic deficiency in cultured skin fibroblasts. This deficiency suggested a defect in the intracellular sorting pathway of this enzyme. The sequence analysis of the gene encoding LIMP-2 (SCARB2), the sorting receptor for beta-glucocerebrosidase, confirmed this hypothesis. A homozygous nonsense mutation in codon 178 of SCARB2 was found in the patient, whereas her healthy parents were heterozygous for the mutation. Besides lacking immunodetectable LIMP-2, patient fibroblasts also had decreased amounts of beta-glucocerebrosidase, which was mainly located in the endoplasmic reticulum, as assessed by its sensitivity to Endo H. This is the first report of a mutation in the SCARB2 gene associated with a human disease, which, contrary to earlier proposals, shares no features with Charcot-Marie-Tooth disease both at the clinical and neurophysiological levels.

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URI

http://hdl.handle.net/10400.16/885

Contexto Educativo

Citação

Hum Mol Genet. 2008 Jul 15;17(14):2238-43

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Fascículo

Editora

Oxford University Press,

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SN - Artigos publicados em revistas indexadas na Pubmed/Medline
G - Artigos publicados em revistas indexadas na Medline
SNEF - Artigos publicados em revistas indexadas na Pubmed/Medline
SNF - Artigos publicados em revistas indexadas na Pubmed/Medline
SNOS - Artigos publicados em revistas indexadas na Medline
SNU - Artigos publicados em revistas indexadas na Medline

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